Papers of the Week

The deletion of exon 18 from Col17a1 in transgenic ΔNC14A mice results in the absence of the NC14A, which corresponds to the human NC16A domain, the immunodominant epitope in bullous pemphigoid. Before the age of one year 84% of ΔNC14A mice have developed severe itch and skin erosion. Further characterization of mice with mutated collagen XVII (ColXVII/BP180) revealed acanthosis, subepidermal blistering and inflammatory cell infiltrate, especially neutrophils, eosinophils and mast cells in the lesional skin. Direct immunofluorescence analysis detected linear C3, IgG and/or IgA deposition in the dermo-epidermal junction of symptomatic ΔNC14A mice. Elevated gene expression of IL-17-associated cytokines was detected in the lesional skin. An increased proportion of dendritic cells, myeloid-derived suppressor cells and NK cells and the decrease of T cells were found in both the spleen and lymph nodes of symptomatic ΔNC14A mice. The proportions of B cells and Tregs were increased in lymph nodes. An 8-week treatment with an anti-IL-17A decreased the expression of Il6, Il23a and Cxcl1 in the nonlesional skin. Our results suggest that the absence of the NC14A domain of ColXVII in mice causes an autoimmune response against the cutaneous basement membrane and manifests as an IL-17-associated inflammation in the skin.